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Half of New Zealand's birds have gone extinct since humans arrived on the islands. Many more are threatened. Now, researchers reporting in the journal Current Biology on August 5 estimate that it would take approximately 50 million years to recover the number of bird species lost since humans first colonized New Zealand.

"The conservation decisions we make today will have repercussions for millions of years to come," says Luis Valente (@evo_island) of Museum für Naturkunde in Berlin. "Some people believe that if you leave nature alone it will quickly recuperate, but the reality is that, at least in New Zealand, nature would need several million years to recover from human actions--and perhaps will never really recover."

The biodiversity observed today is the result of millions of years of evolutionary time, Valente explains. Extinctions caused by human activities erase this history. While the number of lost or threatened bird species often has been quantified, the broad-scale evolutionary consequences of human impact on island biodiversity rarely have been measured.

In the new study, Valente and colleagues developed a method to estimate how long it would take for islands to regain the number of species lost due to humans. They realized that New Zealand birds would be an ideal system to apply and demonstrate this new method.

"The anthropogenic wave of extinction in New Zealand is very well documented, due to decades of paleontological and archaeological research," Valente says. "Also, previous studies have produced dozens of DNA sequences for extinct New Zealand birds, which were essential to build datasets needed to apply our method."

Using computers to simulate a range of human-induced extinction scenarios, the researchers found that it would take approximately 50 million years to recover the number of species lost since human's first arrived in New Zealand. If all species currently under threat are allowed to go extinct, they report, it would require about 10 million years of evolutionary time to return to the species numbers of today.

Valente says they now plan to estimate evolutionary return times for several islands worldwide to see whether there are certain islands that have more evolutionary time under threat. They also want to assess which anthropogenic factors play the most significant role in determining those losses.

For New Zealand, Valente says, there is a bright side. "The conservation initiatives currently being undertaken in New Zealand are highly innovative and appear to be efficient and may yet prevent millions of years of evolution from further being lost," he says.

Seaweed may be a quiet achiever when it comes to mitigation of greenhouse gases, with it now shown to travel far and deep beyond coastal areas and thus to play a key role in sequestering carbon from the atmosphere.

Seaweed, or macroalgae, form the most extensive and productive vegetated coastal habitats. They colonize all latitudes and are efficient at capturing atmospheric CO2 and converting it into plant material. An international research team has reported that a diverse range of macroalgae species drifts as much as 5000 kilometers beyond coastal areas. Around 70 percent of this seaweed, therefore carbon, will sink to ocean depths below 1000 meters, meaning the carbon is unlikely to return to the atmosphere.

"This finding has huge implications for how the global carbon dioxide budget is calculated," says Ph.D. student, Alejandra Ortega, the first author of the study. "It indicates that macroalgae are important for carbon sequestration and should be included in assessments of carbon accumulated in the ocean, known as blue carbon."

Macroalgae are ignored in current assessments of blue carbon, mainly because these rootless marine plants do not remain in the same place but drift with currents and tides. Little was known about their fate once they have floated away from the coast. As a result, there have been no detailed assessments of their role in carbon sequestration in coastal habitats, particularly in the sediments of seagrass and mangrove.

Now the team, led by Carlos Duarte and his KAUST colleagues at the Red Sea Research Center and the Computational Bioscience Research Center (CBRC), has identified DNA sequences of macroalgae in hundreds of metagenomes generated by the global ocean expeditions Tara Oceans and Malaspina, the later led by Duarte. The expeditions surveyed the global ocean to a depth of 4000 meters and sequenced the particulate material collected in the water sample to create a global DNA resource. The marine scientists searched for macroalgae in these global ocean metagenomes, using Dragon Metagenomic Analysis Platform (DMAP). Developed by CBRC bioinformaticians, DMAP uses KAUST's supercomputer to annotate and compare metagenomic data sets.

For the very first time, the team was able to provide semiquantitative evidence of the presence of macroalgae beyond the shoreline. "Work is still needed to be able to translate a specific amount of DNA into a specific amount of organic carbon in a specific taxon, but finding macroalgal DNA is the first step," says Ortega.

ROCHESTER, Minn. -- Medical doctors in the United States are twice as likely to experience symptoms of burnout as other workers, which can compromise quality of care and place patients at risk. In a study in JAMA Internal Medicine, Mayo Clinic researchers suggest a new approach to fighting burnout: external professional coaching.

Defined by the World Health Organization as "feelings of energy depletion or exhaustion; increased mental distance from one's job, or feelings of negativism or cynicism related to one's job; and reduced professional efficacy," burnout creates problems for both physicians and the patients they treat. This study, led by Liselotte Dyrbye, M.D. and Colin West, M.D., Ph.D., investigates the use of external professional coaching--focused on professional goal setting, work choices, professional relationships, and influencing change at work--to reduce burnout. Though researchers have previously studied coaching in other contexts, this is the first study specifically exploring its effects on physician burnout.

"Helping physicians navigate career decisions and manage the stress of their job is crucial," says Dr. Dyrbye. "While many of these doctors have a good informal support system, professional coaches can address a variety of topics and needs, and provide a safe setting to admit perceived vulnerabilities and uncertainties. We really think it can improve physicians' ability to manage their careers and change the detrimental aspects of their work environments, so that ultimately they can do their job well without feeling overwhelmed."

Participants - 88 practicing physicians - began the study by filling out several self-assessment questionnaires, querying for burnout, quality of life, resilience, and job satisfaction. They then completed 6 sessions with a non-physician credentialed professional coach, who worked with the doctors on issues of their choice. After those six sessions, the physicians filled out the same questionnaires to chart their progress.

Results were promising. The doctors reported less burnout and a higher quality of life after coaching, as compared to before. Notably, the researchers also administered these tests on physicians who were not coached. Across the same span of time, these physicians actually reported more emotional exhaustion and lower quality of life, showing how these symptoms can worsen if left unaddressed.

More research remains to be done on the efficacy of professional coaching when combined with other programs, but these results suggest it may be added to a growing list of evidence-based tools to support physicians and, by extension, the patients they serve. While useful, professional coaching should be offered in parallel to organizational efforts to improve the practice environment and address the underlying drivers of burnout among physicians.

CHAMPAIGN, Ill. -- While watching the production of porous membranes used for DNA sorting and sequencing, University of Illinois researchers wondered how tiny steplike defects formed during fabrication could be used to improve molecule transport. They found that the defects - formed by overlapping layers of membrane - make a big difference in how molecules move along a membrane surface. Instead of trying to fix these flaws, the team set out to use them to help direct molecules into the membrane pores.

Their findings are published in the journal Nature Nanotechnology.

Nanopore membranes have generated interest in biomedical research because they help researchers investigate individual molecules - atom by atom - by pulling them through pores for physical and chemical characterization. This technology could ultimately lead to devices that can quickly sequence DNA, RNA or proteins for personalized medicine.

In 2014, University of Illinois physics professor Aleksei Aksimentiev and graduate student Manish Shankla demonstrated a graphene membrane that controlled a molecule's movement through a nanopore by means of electrical charge. They discovered that once the molecules are on the surface of the membrane, it is very difficult to get them to shuffle into the membrane's pores because molecules like to stick to the surface.

While on sabbatical at Delft University of Technology in the Netherlands, Aksimentiev found that DNA tends to accumulate and stick along the edges of fabrication-formed defects that occur as linear steps spanning across the membrane's surface. The Illinois team's goal was to find a way to use these flaws to direct the stuck molecules into the nanopores, as a principle that can also apply to the delivery, sorting and analysis of biomolecules.

To refine and confirm their observations, the researchers used the Blue Waters supercomputer at the National Center for Supercomputing Applications at Illinois and the XSEDE supercomputer to model the system and molecule movement scenarios at the atomic level.

"Molecular dynamics simulations let us watch what is happening while simultaneously measuring how much force is required to get the molecule to clear a step," Aksimentiev said. "We were surprised to find that it takes less force to move a molecule down a step than up. Although it may seem intuitive that gravity would make stepping down easier, it is not the case here because gravity is negligible at the nanoscale, and the force required to move up or down should be the same."

Aksimentiev said team members originally thought they could use concentric defect patterns that form around the pores to force the molecules down, but their simulations showed the molecules congregating along the edges of the steps. That is when it dawned on them: A defect with edges that spiral into a pore, combined with an applied directional force, would give the molecule no other option than to go into the pore - kind of like a drain.

"This way, we can drop molecules anywhere on the membrane covered with these spiral structures and then pull the molecules into a pore," he said.

The researchers have not yet produced a membrane with spiral defects in the laboratory, but that task may be easier than trying to rid a graphene membrane of the current molecule-immobilizing step defects, they said.

"When manufactured at scale, defect-guided capture may potentially increase the DNA capture throughput by several orders of magnitude, compared with current technology," Shankla said.

"After a long development process, we are excited to see this principle used in a variety of other materials and applications such as delivery of individual molecules to reaction chambers for experiments," the researchers said.

All living organisms depend on enzymes - molecules that speed up biochemical reactions that are essential for life.

Scientists have spent decades trying to create artificial enzymes capable of cranking out important chemicals and fuels at an industrial scale with performance rivaling their natural counterparts.

Researchers from Stanford University and SLAC National Accelerator Laboratory have developed a synthetic catalyst that produces chemicals much the way enzymes do in living organisms. In a study published in the Aug. 5 issue of Nature Catalysis, the researchers say their discovery could lead to industrial catalysts capable of producing methanol using less energy and at a lower cost. Methanol has a variety of applications, and there is a growing demand for its use as a fuel with lower emissions than conventional gasoline.

"We took our inspiration from nature," said senior author Matteo Cargnello, an assistant professor of chemical engineering at Stanford. "We wanted to mimic the function of natural enzymes in the laboratory using artificial catalysts to make useful compounds."

For the experiment, the researchers designed a catalyst made of nanocrystals of palladium, a precious metal, embedded in layers of porous polymers tailored with special catalytic properties. Most protein enzymes found in nature also have trace metals, like zinc and iron, embedded in their core.

The researchers were able to observe trace palladium in their catalysts with electron microscopic imagery by co-author Andrew Herzing of the National Institute of Standards and Technology.

Model reaction

"We focused on a model chemical reaction: converting toxic carbon monoxide and oxygen into carbon dioxide (CO2)," said PhD student Andrew Riscoe, lead author of the study. "Our goal was to see if the artificial catalyst would function like an enzyme by speeding up the reaction and controlling the way CO2 is produced."

To find out, Riscoe placed the catalyst in a reactor tube with a continuous flow of carbon monoxide and oxygen gas. When the tube was heated to about 150 degrees Celsius (302 degrees Fahrenheit), the catalyst began generating the desired product, carbon dioxide.

High-energy X-rays from the Stanford Synchrotron Radiation Lightsource (SSRL) at SLAC revealed that the catalyst had traits similar to those seen in enzymes: The palladium nanocrystals inside the catalyst were continuously reacting with oxygen and carbon monoxide to produce carbon dioxide. And some of the newly formed carbon dioxide molecules were getting trapped in the outer polymer layers as they escaped from the nanocrystals.

"The X-rays showed that once the polymer layers were filled with CO2, the reaction stopped," said Cargnello, an affiliate with the Stanford Natural Gas Initiative (NGI). "This is important, because it's the same strategy used by enzymes. When an enzyme produces too much of a product, it stops working, because the product is no longer needed. We showed that we can also regulate the production of CO2 by controlling the chemical composition of the polymer layers. This approach could impact many areas of catalysis."

The X-ray imaging was conducted by study co-authors Alexey Boubnov, a Stanford postdoctoral scholar, and SLAC scientists Simon Bare and Adam Hoffman.

Making methanol

With the success of the carbon dioxide experiment, Cargnello and his colleagues have turned their attention to converting methane, the main ingredient in natural gas, into methanol, a chemical widely used in textiles, plastics and paints. Methanol has also been touted as a cheaper, cleaner alternative to gasoline fuel.

"The ability to convert methane to methanol at low temperatures is considered a holy grail of catalysis," Cargnello said. "Our long-term goal is to build a catalyst that behaves like methane monooxoygenase, a natural enzyme that certain microbes use to metabolize methane."

Most methanol today is produced in a two-step process that involves heating natural gas to temperatures of about 1,000 C (1,800 F). But this energy-intensive process emits a large amount of carbon dioxide, a potent greenhouse gas that contributes to global climate change.

"An artificial catalyst that directly converts methane to methanol would require much lower temperatures and emit far less CO2," Riscoe explained. "Ideally, we could also control the products of the reaction by designing polymer layers that trap the methanol before it burns."

Future enzymes

"In this work, we demonstrated that we can prepare hybrid materials made of polymers and metallic nanocrystals that have certain traits typical of enzymatic activity," said Cargnello, who is also affiliated with Stanford's SUNCAT Center for Interface Science and Catalysis. "The exciting part is that we can apply these materials to lots of systems, helping us better understand the details of the catalytic process and taking us one step closer to artificial enzymes."

Some older adults without noticeable cognitive problems have a harder time than younger people in separating irrelevant information from what they need to know at a given time, and a new Johns Hopkins University study could explain why.

The findings offer an initial snapshot of what happens in the brain as young and old people try to access long-term memories, and could shed light on why some people's cognitive abilities decline with age while others remain sharp.

"Your task performance can be impaired not just because you can't remember, but because you can't suppress other memories that are irrelevant," said senior author Susan Courtney, a cognitive neuroscientist at Johns Hopkins. "Some 'memory problems' aren't a matter of memory specifically, but a matter of retrieving the correct information at the right time to solve the problem at hand."

The findings were just posted in Neurobiology of Aging.

The researchers had 34 young adults (18 to 30) and 34 older adults (65-85) perform a mental arithmetic task while their brain activity was measured through functional magnetic resonance imaging, or fMRI. Other images were also collected to measure the integrity of the connections between brain areas called white matter tracts.

The task compared the participants' ability to inhibit irrelevant information automatically retrieved from long term memory. They were asked to indicate whether a proposed solution to an addition or multiplication problem was correct or not - for instance 8x4=12 or 8+4=32. These examples would create interference as participants considered the right answer because although they should answer "incorrect," the proposed solution seems correct at first glance, based on long-term memories of basic math. This interference did not exist when participants were asked to answer clearly false equations like 8x4=22. Making the task even more complicated, the subjects were sometimes asked to switch to multiplication after they saw the addition symbol and vice versa.

Older people were a fraction of a second slower at answering the questions than younger participants, particularly when there was interference, but the more dramatic difference showed up in the brain scans. Older individuals who had more difficulty with interference also had more frontal brain activation than young adults.

The brain imaging demonstrated that in some aging participants, fibers connecting the front and back of the brain appear to have been damaged over the years. However other older individuals had fibers similar to much younger subjects. The greater the integrity of these fibers, the better the participant's task performance, said lead author Thomas Hinault, a postdoctoral fellow at Johns Hopkins.

"Everyone we studied had good functioning memory, but still we saw differences," Hinault said. "There are so many disruptions in the world and being able to suppress them is crucial for daily life."

The researchers were surprised to find that during parts of the task that were the trickiest, where participants had to switch between multiplication and addition and were asked to add after they saw a multiplication command or vice versa, the people with the strongest brain fiber connections counterintuitively performed even better. Something about deliberately exercising the mind in this fashion made the most agile minds even more so.

"If you have good connections between brain networks, that will help," Courtney said. "If not, you have interference."

BEER-SHEVA, Israel...August 5, 2019 - Mankai, a new high-protein aquatic plant strain of duckweed, has significant potential as a superfood and provides glycemic control after carbohydrate consumption, a team of researchers from Ben-Gurion University of the Negev (BGU) has determined.

Hila Zelicha, a registered dietician (R.D.) and Ph.D. student in the BGU Department of Public Health and her BGU colleagues researched the glycemic aspect of Mankai duckweed. Her research was just published in Diabetes Care, the official journal of the American Diabetes Association.

In this new study, the researchers compared Mankai shake consumption to a yogurt shake equivalent in carbohydrates, protein, lipids, and calories. Following two weeks of monitoring with glucose sensors, participants who drank the duckweed shake showed a much better response in a variety of measurements including lower glucose peak levels; morning fasting glucose levels; later peak time; and faster glucose evacuation. The participants also felt more full.

The research group, led by Prof. Iris Shai, a member of BGU's S. Daniel Abraham International Center for Health and Nutrition and the School of Public Health, has found in several previous studies that Mankai duckweed has tremendous health potential as a superfood. This new research is a sub-study of the Dietary Intervention Randomized Controlled Trial - Polyphenols Unprocessed (DIRECT PLUS) which explores the effects of green- Mediterranean diet.

The Mankai duckweed aquatic plant is being grown in Israel and other countries in a closed environment and is highly environmentally sustainable - requiring a fraction of the amount of water to produce each gram of protein compared to soy, kale or spinach. It can also be grown year-round using hydroponic cultivation, which is another advantage.

Duckweed has been consumed for hundreds of years in Southeast Asia, where it is known as "vegetable meatball" due to its high-protein content -- more than 45% of the dry matter. It includes the complete protein profile of eggs, containing all nine essential and six conditional amino acids. In addition, Mankai is very rich in polyphenols, mainly phenolic acids and flavonoids (including catechins), dietary fibers, minerals (including iron and zinc), vitamin A, vitamin B complex, and vitamin B12 , which is rarely produced by plants.

A previous duckweed study conducted by Alon Kaplan, a Ph.D. student in Prof. Shai's lab, published in Clinical Nutrition, showed that the absorption of the essential amino acids from Mankai was similar to the soft cheese and plant (peas) equivalent in protein content, reinforcing its role as a high-quality protein source. Also, the study suggested that Mankai is a unique plant source of vitamin B12.

Another study by the researchers in the Journal of Nutrition published earlier this year by BGU Ph.D. student Anat Yaskolka Meir R.D., indicates that a Mediterranean diet with Mankai, elevates iron and folic acid levels, despite low quantities of red meat. This study also determined that iron from Mankai was efficient in treating iron-deficiency anemia in anemic rats to the same degree as the common treatment.

It is the aggregation of all of these properties which seem to make the easily integratable, tasteless and odorless plant, a good candidate to become a superfood. Harvard University apparently agrees, Mankai smoothies were introduced in the Harvard School of Public Health cafeteria recently.

A new team-based model for intensive care unit (ICU) pharmacists, developed by Rutgers and RWJBarnabas Health System, resolves a common dilemma for hospitals and improves care for critically ill patients.

Many ICUs include a team of general practice pharmacists, supplemented by one who specializes in critical care. Typically, only the specialist can respond to such complex, ICU-specific issues as determining whether a delirious patient needs to switch medications. But when the specialist is not on duty, patients often have to wait longer for that expert care, according to the study published in the Journal of Clinical Outcomes Management.

Lead researcher Liza Barbarello Andrews, a clinical associate professor at Rutgers University's Ernest Mario School of Pharmacy, developed a solution at Robert Wood Johnson University Hospital Hamilton, where she is the sole critical care pharmacy specialist.

Under her new model, several non-specialists on the Hamilton ICU's pharmacy staff underwent six months of intensive classroom and clinical training on topics such as the complications that patients face while attached to mechanical ventilators; infectious disease risk; and blood flow management for non-mobile patients. Over time, all pharmacists on the newly formed Critical Care Pharmacist Team (CCPT) were able to provide the full range of patient interventions previously limited to the critical care specialist.

The new model, believed to be the first of its kind, produced notable results: The overall quality of pharmacy services provided to patients improved. All pharmacists who underwent the training reported feeling comfortable and confident in providing the specialized levels of care, along with a greater sense of professional satisfaction. Other members of the ICU staff, including physicians and nurses, also reported improvements in pharmacy care, including a consistent, high level of care even when the specialist was not on duty.

"Before we tried this model, the non-specialty pharmacists in the ICU were often uncomfortable with clinical issues, which sometimes meant going to the bedside to assess the situation. As a result, relatively minor issues were frequently escalated with a call to the specialist, who was not always readily available," Andrews said. "Our new model effectively empowers all of our pharmacists to act as specialists."

Andrews said the new model was adopted without significant cost and should therefore benefit other community-based hospitals with limited resources.

Given that they generate hardly any greenhouse gases, are undemanding, nutritious and fast growing, insects have generated a lot of hype in recent years. They are touted as the superfood of the future - cheap suppliers of protein that can even decompose all kinds of residual products.

"This all sounds very promising, but has little to do with reality," says Wilhelm Windisch, Professor of Animal Nutrition at the Technical University of Munich. "Anyone who hopes to keep animals professionally and on a large scale needs to know exactly what kinds of nutrients they need and can consume. And for insects, this is yet to be determined."

In collaboration with a German-Kenyan research team, the agricultural scientist has for the first time ever systematically investigated how various feed substrates influence the growth and development of crickets (Gryllus bimaculatus) and locusts (Schistocerca gregaria).

From biblical plague to farm animal

In the wild, both species feed on leaves. "But supplying large insect farms with fresh greens year-round is virtually impossible to implement," says Windisch. "You need feed of verifiable quality and safety that can be dried, stored and transported."

Commercial animal feed would fulfill these criteria. But, does it meet the nutritional needs of insects? At the renowned Centre of Insect Physiology and Ecology (ICIPE) in Nairobi, the team investigated how the two species responded to different feed choices.

They tested different dry feed variants containing cornstarch, protein and fiber-rich cowpea leaves, protein-rich soy extract and vitamin-enriched carrot powder.

The researchers logged the amount of feed provided every day, weighed the excrements and finally determined the average weight of the adult insects. Two rounds of tests were carried out and evaluated over a three-month period.

The goal: Nutritional recommendations for grasshoppers and co.

"The result surprised us," recalls Windisch: "It was clear to us that the metabolism and digestion are rather different in insects than in conventional farm animals such as cattle, pigs and chickens. What we did not expect were immense species-specific differences."

Locusts, for example, can process plant fibers that are indigestible by humans. Crickets, on the other hand, excrete fiber-rich food. Locusts grow quickly only when fed protein, while crickets need starch, above all.

The source of the differences is still unclear. In their next project, the researchers hope to investigate which enzymes are active in the intestines of various insects and which of them can, for example, convert plant fiber into glucose.

"The research is still in its infancy, but with each result we understand the metabolism and nutrient needs of individual genera better and can use the outcomes in professional insect farms to process biomass that, for example, could not be used previously because it is inedible for humans and livestock can process it poorly, at best," sums up Windisch.

Tomato yellow leaf curl disease (TYLCD) caused by tomato yellow leaf curl virus-like viruses is the most destructive disease of tomato, causing severe damage to crops worldwide and resulting in high economic losses. To combat this disease, many farmers opt for intensive application of insecticides. However, this practice is frequently ineffective and has a negative impact on the environment and human health.

Alternatively, some farmers plant TYLCD-resistant tomato varieties, but these hybrid varieties are often tasteless and a poor comparison to the robust flavor of traditional tomatoes. As a result, there is a demand for effective and environmentally friendly control measures to prevent continuing widespread damage of TYLCD, as well as other plant viruses.

To answer this demand, a team of scientists at the Spanish Council of Scientific Research (IHSM UMA-CSIC) conducted field and greenhouse trials for three consecutive years and found two environmentally friendly control alternatives to insecticides.

First, they discovered that protecting tomato crops with UV-blocking plastics led to reduced TYLCD damage. Secondly, they found that the application of a salicylic acid analogue to strengthen tomato plant defenses was also effective in reducing TYLCD-associated losses.

For the most effective results, the team recommends that farmers combine both control practices. These practices are proposed for commercial use in open field or on protected tomato crops. These findings also suggest the possibility for future discovery of environmentally friendly virus control strategies.

HOUSTON - (Aug. 5, 2019) - Paper is at the heart of an experimental device developed by Rice University bioengineers to study heart disease.

They are using paper-based structures that mimic the layered nature of aortic valves, the tough, flexible tissues that keep blood flowing through the heart in one direction only. The devices allow the engineers to study in detail how calcifying diseases slow or stop hearts from functioning.

The work by the Brown School of Engineering team, detailed in Acta Biomaterialia, shows that collagen 1, a natural protein and a component of the valves' fibrous extracellular matrix, appears to have a strong association with calcification when it is found outside its usual domain. Valves hardened by calcium deposits are less flexible and lose their ability to seal the heart's chambers.

"When tissues make a lot of excess type 1 collagen, it's called fibrosis," said Rice bioengineer Jane Grande-Allen, who directed the study with Rice graduate student and lead author Madeline Monroe. "Fibrosis can happen in many types of tissues and it accompanies calcific aortic valve disease (CAVD). That doesn't necessarily mean collagen will always cause CAVD, but it definitely drove the calcification-linked phenotype in the cells that we cultured."

Collagen generally stays in the valve's fibrosa layer, one of three in each of the three leaflets that make up an aortic valve. (The others layers are the spongiosa and ventricularis.) The researchers prepared paper layers to support heart valve cells embedded in either collagen or hyaluronan, and discovered that when collagen 1 proteins are present in multiple layers, the cells behave in a way that would ultimately lead to mineralized lesions.

Grande-Allen said the layers of extracellular matrix in a healthy aortic valve are well-defined. "In a more pathological state, the collagen isn't localized," she said. "It's spread out. Our models suggest nonlocalized collagen could contribute to cell overexpression of these calcific factors."

The Rice researchers want to know how that happens. They needed a way to see how valve cells would react to collagen spreading through a three-dimensional tissue, and common filter paper turned out to be a suitable stand-in. What they made doesn't look like a heart valve, but effectively acts like one to show how cells proliferate through a valve's layers.

Heart valve disease can't be treated with a pill yet, said Grande-Allen, who has studied valve disease for much of her career and reported on paper-based cultures in 2015. Current remedies often involve replacement of the valve with human or animal donor tissue or a mechanical valve. But the ability to accurately model and manipulate all the layers of a valve could help decipher the chemical transactions in heart disease. She said that may eventually lead to noninvasive medication.

"The first step has been to develop models that mimic the way the cells in valves behave," Grande-Allen said. "The next step would be to see them actually calcify. Once that is in hand, we can start to test chemicals that would block that calcification process."

Monroe, with co-author and Rice undergraduate Rebecca Nikonowicz and early help from alumnus Matthew Sapp, took inspiration from the cells-in-gels-in-wells filter-paper cultures used at Harvard University to study hypoxia in lung cancer cells.

The Rice lab started by 3D-printing polymer holders with arrays of holes. These held in place layers of paper that had been impregnated with a wax pattern to eliminate crosstalk between the open circles of filter paper. The circles were then saturated with various combinations of fibrous collagen 1, hyaluronan (normally found in the spongiosa layer) and millions of living heart cells, and the sheets were pressed together within the holders.

"This modeling system gives us complete control over a lot of different variables," Monroe said. "We were able to create distinct stacks with different compositions based on what components we put in each layer. We had stacks where all the layers were all hyaluronan, or all collagen, or heterogeneous stacks with both kinds of layers.

"That let us see if the cells behaved differently when there was an increase in the number of collagen layers," she said.

Monroe assessed the cells' behavior over time by analyzing the protein markers they expressed, particularly alpha smooth muscle actin (aSMA), a Runt-related transcription factor-2 (RunX2) and SRY-box 9 (Sox9), all of which are indicators for CAVD. Using a high-throughput staining and scanning method with the groups of wells allowed her to quickly gather data from dozens of structures.

The data let them see that valvular interstitial cells, the principal and normally stable aortic valve cell type, became more susceptible to osteogenesis -- hardening -- in the presence of more layers containing collagen protein.

"The paper model is ingenious for allowing us that versatility and flexibility," Grande-Allen said. "I don't know of another method that so easily allows us to put together different layers easily, culture the combinations together and then take them apart and analyze them so rapidly."

Environmental defenders on the front line of natural resource conflict are being killed at an alarming rate, according to a University of Queensland study.

According to UQ School of Biological Sciences researcher Dr Nathalie Butt, the 1558 deaths recorded between 2002 and 2017 were largely due to external demand for the very resources they were trying to protect.

"The number of reported deaths of environmental defenders has increased, as well as the number of countries where they occur," Dr Butt said.

"Environmental defenders help protect land, forests, water and other natural resources.

"They can be anyone - community activists, lawyers, journalists, members of social movements, NGO staff and Indigenous people - anyone who resists violence.

"And importantly, Indigenous peoples are dying in higher numbers than any other group."

The reasons for the fatal violence are mainly related to conflict over natural resources, such as water, timber, land for agriculture or development, or minerals.

A third of all deaths between 2014 and 2017 - more than 230 - were linked to the mining and agribusiness sectors.

"Although conflict over natural resources is the underlying cause of the violence, spatial analyses showed corruption was the key correlate for the killings," Dr Butt said.

"Globally, 43 per cent of all murders result in a conviction, while for environmental defenders this figure is only 10 per cent.

"In many instances, weak rule of law means that cases in many countries are not properly investigated, and sometimes it's the police or the authorities themselves that are responsible for the violence.

"For example, in Pau D'Arco, Brazil, ten land defenders were killed by the police in May 2017."

Dr Butt is calling for more transparency and accountability from multinational companies and governments, and awareness from consumers.

"The ecology of the planet is fundamental to the production of food and resources - that we all depend upon - and we are ultimately bound to support it, otherwise it will not support us," she said.

"Part of this support is to protect the people who protect it.

"As consumers in wealthy countries - who are effectively outsourcing our resource consumption - we share responsibility for what's happening.

"Businesses, investors and national governments at both ends of the chain of violence need to be more accountable."

MADISON - Along with flying and invisibility, high on the list of every child's aspirational superpowers is the ability to see through or around walls or other visual obstacles.
That capability is now a big step closer to reality as scientists from the University of Wisconsin-Madison and the Universidad de Zaragoza in Spain, drawing on the lessons of classical optics, have shown that it is possible to image complex hidden scenes using a projected "virtual camera" to see around barriers.

The technology is described in a report today (Aug. 5, 2019) in the journal Nature. Once perfected, it could be used in a wide range of applications, from defense and disaster relief to manufacturing and medical imaging. The work has been funded largely by the military through the U.S. Defense Department's Advanced Research Projects Agency (DARPA) and by NASA, which envisions the technology as a potential way to peer inside hidden caves on the moon and Mars.

Technologies to achieve what scientists call "non-line-of-sight imaging" have been in development for years, but technical challenges have limited them to fuzzy pictures of simple scenes. Challenges that could be overcome by the new approach include imaging far more complex hidden scenes, seeing around multiple corners and taking video.

"This non-line-of sight imaging has been around for a while," says Andreas Velten, a professor of biostatistics and medical informatics in the UW School of Medicine and Public Health and the senior author of the new Nature study. "There have been a lot of different approaches to it."

The basic idea of non-line of-sight imaging, Velten says, revolves around the use of indirect, reflected light, a light echo of sorts, to capture images of a hidden scene. Photons from thousands of pulses of laser light are reflected off a wall or another surface to an obscured scene and the reflected, diffused light bounces back to sensors connected to a camera. The recaptured light particles or photons are then used to digitally reconstruct the hidden scene in three dimensions.

"We send light pulses to a surface and see the light coming back, and from that we can see what's in the hidden scene," Velten explains.

Recent work by other research groups has focused on improving the quality of scene regeneration under controlled conditions using small scenes with single objects. The work presented in the new Nature report goes beyond simple scenes and addresses the primary limitations to existing non-line-of-sight imaging technology, including varying material qualities of the walls and surfaces of the hidden objects, large variations in brightness of different hidden objects, complex inter-reflection of light between objects in a hidden scene, and the massive amounts of noisy data used to reconstruct larger scenes.

Together, those challenges have stymied practical applications of emerging non-line-of-sight imaging systems.

Velten and his colleagues, including Diego Gutierrez of the Universidad de Zaragoza, turned the problem around, looking at it through a more conventional prism by applying the same math used to interpret images taken with conventional line-of-sight imaging systems. The new method surmounts the use of a single reconstruction algorithm and describes a new class of imaging algorithms that share unique advantages.

Conventional systems, notes Gutierrez, interpret diffracted light as waves, which can be shaped into images by applying well known mathematical transformations to the light waves propagating through the imaging system.

In the case of non-line-of-sight imaging, the challenge of imaging a hidden scene, says Velten, is resolved by reformulating the non-line-of-sight imaging problem as a wave diffraction problem and then using well-known mathematical transforms from other imaging systems to interpret the waves and reconstruct an image of a hidden scene. By doing this, the new method turns any diffuse wall into a virtual camera.

"What we did was express the problem using waves," says Velten, who also holds faculty appointments in UW-Madison's Department of Electrical and Computer Engineering and the Department of Biostatistics and Medical Informatics, and is affiliated with the Morgridge Institute for Research and the UW-Madison Laboratory for Optical and Computational Instrumentation. "The systems have the same underlying math, but we found that our reconstruction is surprisingly robust, even using really bad data. You can do it with fewer photons."

Using the new approach, Velten's team showed that hidden scenes can be imaged despite the challenges of scene complexity, differences in reflector materials, scattered ambient light and varying depths of field for the objects that make up a scene.

The ability to essentially project a camera from one surface to another suggests that the technology can be developed to a point where it is possible to see around multiple corners: "This should allow us to image around an arbitrary number of corners," says Velten. "To do so, light has to undergo multiple reflections and the problem is how do you separate the light coming from different surfaces? This 'virtual camera' can do that. That's the reason for the complex scene: there are multiple bounces going on and the complexity of the scene we image is greater than what's been done before."

According to Velten, the technique can be applied to create virtual projected versions of any imaging system, even video cameras that capture the propagation of light through the hidden scene. Velten's team, in fact, used the technique to create a video of light transport in the hidden scene, enabling visualization of light bouncing up to four or five times, which, according to the Wisconsin scientist, can be the basis for cameras to see around more than one corner.

The technology could be further and more dramatically improved if arrays of sensors can be devised to capture the light reflected from a hidden scene. The experiments described in the new Nature paper depended on just a single detector.

In medicine, the technology holds promise for things like robotic surgery. Now, the surgeon's field of view is restricted when doing sensitive procedures on the eye, for example, and the technique developed by Velten's team could provide a more complete picture of what's going on around a procedure.

In addition to helping resolve many of the technical challenges of non-line-of-sight imaging, the technology, Velten notes, can be made to be both inexpensive and compact, meaning real-world applications are just a matter of time.

Bottom Line: Incorporation of pan-cancer microsatellite instability (MSI) detection into the 74-gene panel Guardant360 liquid biopsy assay showed high concordance with matched tissue samples in nearly 1,000 patients.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Authors: Martina Lefterova, MD, PhD, laboratory director and medical director at Guardant Health in Redwood City, California; and Scott Kopetz, MD, PhD, associate professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center

Background: "Following the tissue-agnostic approval of pembrolizumab for patients with MSI-high tumors, a barrier to improved outcomes for many patients is the awareness and testing of MSI status," said Kopetz.

Evaluation of MSI status, which is typically performed via tumor biopsy, is underutilized for several reasons, noted Kopetz. Reasons include the inherent invasive nature of traditional biopsies, which may not be feasible in some patients; a lack of viable tissue, which may be required for other analyses; and a lack of routine testing, as MSI-high tumors are relatively rare, he noted. "The addition of MSI detection into a routine, noninvasive sequencing panel following the diagnosis of metastatic cancer could direct clinicians to prescribe immunotherapy and provide patients with better outcomes," Kopetz said.

How the Study Was Conducted and Results: To develop a pan-cancer MSI detection panel, the researchers identified 90 relevant microsatellite loci to include in the Guardant360 panel. The assay was validated by comparing the MSI status as determined via the liquid biopsy test with the MSI status previously determined via standard-of-care tissue testing on 1,145 patients spanning 40 distinct cancer types.

In 949 evaluable patients, the liquid biopsy test identified 87 percent of patients previously reported as MSI-high and 99.5 percent of patients previously reported as MSI-low or microsatellite-stable, representing an overall accuracy of 98.4 percent.

The researchers also evaluated MSI status using the liquid biopsy test in 28,459 consecutive samples from patients with advanced cancer. Among this cohort, 278 samples representing 16 unique tumor types were identified as MSI-high; MSI prevalence was high in endometrial, colorectal, and gastric cancers, while MSI prevalence was low in lung, bladder, and head and neck cancers, which is consistent with previous reports using tissue samples, noted Lefterova.

Additionally, the researchers evaluated the clinical outcomes of 16 patients with metastatic gastric cancer that had previously progressed following standard-of-care chemotherapy; these patients had MSI-high tumors detected using the liquid biopsy test and were treated with either pembrolizumab (15 patients) or nivolumab (one patient). Among these patients, the objective response rate and disease control rate were 63 percent and 81 percent, respectively, which are comparable to the responses for patients identified as MSI-high through tissue testing, explained Kopetz.

Authors' Comments: "The results from our study show that Guardant360, a liquid biopsy test, can deliver valid MSI-high results that can be used to guide treatment planning for patients with advanced cancer," said Lefterova. "The addition of MSI detection increases the utility of the assay to direct clinicians beyond targeted therapies to include immunotherapies," she said.

"By adding MSI testing into a non-invasive screening panel, clinicians can routinely scan for this prognostic factor without ordering a separate test," added Kopetz.

"Our results show that MSI detection in blood samples is not only possible, but valid and informative for immunotherapy selection in patients with a wide range of advanced solid tumors," said Lefterova.

Study Limitations: As a limitation to the study, of the more than 28,000 plasma samples evaluated for MSI status, only a subset of them were matched to tissue samples, noted Kopetz. Another limitation of the study is that only one liquid biopsy test was studied, and the results cannot be applied more broadly to other tests, noted Lefterova.

Funding & Disclosures: This study was sponsored by Guardant Health. Lefterova is a current employee of Guardant Health. Kopetz declares no conflict of interest.

PITTSBURGH, Aug. 5, 2019 - Scientists at Magee-Womens Research Institute (MWRI), collaborating with clinicians at UPMC Magee-Womens Hospital and UPMC Children's Hospital of Pittsburgh report two cases in which young transgender women attempted to recover their fertility after starting and stopping gender-affirming medications.

The study, published today in Pediatrics, found that one transgender woman was able to produce viable sperm after a few months of discontinuing her puberty-halting medication, whereas a different patient on hormone therapy could not produce sperm during the time she could psychologically tolerate being off her medication.

"We were interested in examining the timeline for getting viable sperm after stopping masculinity-suppressing medication," said lead author Hanna Valli-Pulaski, Ph.D., a research assistant professor at MWRI. "Going on and off gender-affirming medications can cause psychological distress in this population and it's important patients have a discussion with their health care provider before starting or stopping any treatment."

The research team examined medical records of two transgender women who tried to preserve their sperm after stopping hormone therapy and compared their semen quality against eight other transgender women who elected to preserve their sperm before beginning therapy. All of the study participants came through the Fertility Preservation Program in Pittsburgh between 2015 and 2018 as young adults.

One of the patients who elected to preserve their sperm after beginning therapy had been taking the drug Lupron--a sex hormone blocker that halts puberty when taken in adolescence--for six months. She elected to stop taking Lupron to attempt sperm cryopreservation.

Five months later, she was able to produce a sperm sample comparable to those collected from the eight transgender women who saved their sperm prior to undergoing treatment.

Although this one case shows that it's possible to recover sperm after starting gender-affirming therapy, stopping medication for even just a few months can be psychologically distressing, Valli-Pulaski said. For male-to-female transgender individuals, facial hair can start to sprout and the voice begin to deepen after just a few months of stopping medication. It's possible to reverse these effects, but it would take time.

What's more, a second case included in this study showed that fertility doesn't always return quickly after going off gender-affirming drugs.

This patient had been taking estradiol and spironolactone for more than two years. Four months after stopping treatment, she was still unable to produce viable sperm, and at that point, she decided to stop trying for fertility preservation and proceeded with gender reassignment surgery.

The sperm production results of the two study participants provide valuable information that clinicians can share with future patients wishing to have biological children after beginning gender-affirming therapy, notes Valli-Pilaski.

"Right now, there's not much information available about fertility preservation for transgender patients," Valli-Pulaski said. "If you have any data, it's important to share so that patients, researchers and clinicians can learn from it."